11-72757802-C-T

Position:

• chr11-72757802-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006645.3(STARD10):​c.542G>A​(p.Cys181Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STARD10 NM_006645.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.36

Genes affected

STARD10 (HGNC:10666): (StAR related lipid transfer domain containing 10) Predicted to enable lipid binding activity. Predicted to be involved in lipid transport. Predicted to act upstream of or within bile acid secretion and positive regulation of peroxisome proliferator activated receptor signaling pathway. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ARAP1 (HGNC:16925): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1) The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STARD10	NM_006645.3	c.542G>A	p.Cys181Tyr	missense_variant	5/7	ENST00000334805.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STARD10	ENST00000334805.11	c.542G>A	p.Cys181Tyr	missense_variant	5/7	1	NM_006645.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.542G>A (p.C181Y) alteration is located in exon 5 (coding exon 4) of the STARD10 gene. This alteration results from a G to A substitution at nucleotide position 542, causing the cysteine (C) at amino acid position 181 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;T;T;T;T;T;T;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;.;D;D;D;D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.91	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.15	D
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-8.8	D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;.;.;.;D
Polyphen		1.0, 1.0	.;D;D;D;.;.;.;.;.
Vest4		0.92, 0.90
MutPred		0.77		.;Loss of methylation at K179 (P = 0.0881);Loss of methylation at K179 (P = 0.0881);.;.;.;Loss of methylation at K179 (P = 0.0881);.;Loss of methylation at K179 (P = 0.0881);
MVP		0.89
MPC		1.7
ClinPred		1.0	D
GERP RS		3.6
Varity_R		0.93
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1858663557; hg19: chr11-72468847;